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1. How did you become interested in translational gastroenterology?

alessandra.jpgDuring my training as a gastroenterologist I developed a growing interest in Inflammatory Bowel Disease (IBD), a chronic inflammatory disorder of the gut that encompasses Crohn’s disease (CD) and Ulcerative Colitis (UC).  The cause of this serious disorder is unknown, but the available evidence suggests that it is driven by an overactive immune response towards the bacterial flora in genetically susceptible individuals.  Patients are usually treated with immune suppressants and often require surgery during the course of the disease. During my training, I was involved in clinical studies on new radiological tools and therapeutic compounds for the diagnosis and treatment of patients with IBD. However, I soon realised that a better understanding of the disease pathogenesis was needed to improve patients’ management. In 2005, I moved to Oxford to work as a research fellow at the Wellcome Trust for Human Genetics under the supervision of Prof Derek Jewell and was involved in genetic studies in IBD. I became increasingly interested in the pathophysiology of intestinal inflammation and decided to undertake a DPhil in this area under the supervision of Professor Fiona Powrie at the University of Oxford. In particular I evaluated the role of the IL23/IL17 inflammatory pathway in IBD and was able to translate findings from animal models of colitis into human disease. I identified a novel population of innate lymphoid cells that accumulate in the inflamed intestine of patients with CD, where they can contribute to inflammation.

2. What are you currently working on and what importance does your work hold for current patients with gastrointestinal issues?

My current research focuses on the characterization of the host-microbial interactions in patients with IBD and Primary Sclerosing Cholangitis (PSC). PSC is a chronic inflammatory disorder of the liver, characterised by narrowing and scarring of the bile ducts, eventually leading to loss of liver function and need for transplantation. PSC is associated with IBD in 80% of cases. Patients with IBD and PSC have a five times higher risk of developing colon cancer compared to UC alone and are also at increased risk of hepatobiliary malignancy. Unfortunately, the pathogenesis of the disease is unknown and there is no curative treatment for patients. The mechanisms involved in inflammation and increased cancer risk need to be identified in order to develop novel therapeutic strategies. In our project we investigate the role of immune pathways in the pathogenesis of PSC-IBD and how the intestinal microbiota can influence these responses. We characterize the systemic and intestinal immune response in patients with PSC and IBD through a combination of high throughput techniques, including multicolour flow cytometry, CyTOF mass cytometry, molecular biology and in situ analysis. Furthermore, we are using state-of-the-art whole genome shotgun sequencing to investigate both microbiome and patients intestinal transcriptomes and identify novel pathways through which microbial products can influence the host immune function. We aim to test the effects of microbial and host pathways and their interaction on 3-D intestinal in vitro systems (organoids).

3. What do you enjoy most about scientific research?

What I enjoy more about scientific research is the great variety of the work and of the skills required. Scientific research is never boring, days are never the same and routine is unheard of. I love posing questions, making hypothesis and finding answers that are often different from what I had expected and bring me to different project’s directions and unpredicted outcomes. There is always more to learn, more to study, more to investigate. Working in research you develop several skills, from critical thinking and problem solving ability, to technical dexterity, data analysis and effective oral and written communication. Interaction with people, colleagues, scientists, physicians, research nurses etc. is crucial and you develop interpersonal skills and a huge network of collaborators and friends. Finally, I like thinking that our work will contribute to increasing human knowledge, and, in the case of translational research, enhance human health and well-being.

4. What’s the best part of being an Oxford University TGU member?

The Oxford University TGU is the ideal place to be for a clinician scientist like me. There is fantastic interaction and collaboration between physicians, clinical academics and scientists. We have a really efficient system in place for the recruitment of patients to our well-characterised patient cohorts and the collection of tissue and blood samples, together with access to state-of-the-art laboratories and facilities. Finally, we are exposed to the stimulating environment of the Oxford University and to the many possibilities of interdisciplinary collaborations.